Throughout this application various publications are referred to in parenthesis. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference in their entireties into the subject application to more fully describe the art to which the subject application pertains.
The ability to store energy in the form of triglyceride (TG) is conserved from S. cerevisiae to humans. Triglycerides are stored in the cytoplasm surrounded by a monolayer of phospholipid in distinct structures or organelles given numerous names such as lipid particles, oil bodies, adiposomes, eicosasomes, and more commonly lipid droplets (1). Under normal physiological conditions, lipid droplets are involved in maintaining energy balance at the cellular and organismal level; but under conditions of extreme lipid droplet acquisition as in obesity, type II diabetes and cardiovascular diseases may ensue (2-6).
Recently, a great body of information has been generated revealing details of the composition and functions of many of the components of lipid droplets from S. cerevisiae (7), drosophila and mammalian cells (8-10). In mammalian cells, the catabolism of lipid droplets is a highly regulated process involving hormonal signals, droplet structural proteins and lipases (2, 11, 12). While much has been learned about the components and catabolism of lipid droplets, the molecular mechanism of lipid droplet biogenesis remains unknown. The identification of many components of lipid droplets has not revealed obvious proteins that would be involved in their formation. A widely accepted model of lipid droplet biogenesis involves the budding of a single leaflet of the endoplasmic reticulum (ER) membrane with a newly forming core or “lens” of triglyceride (1). The evidence that cytosolic lipid droplets are derived from the ER is based on the findings that some lipid droplet associated proteins are also associated with the ER membrane, and in many instances lipid droplets have been shown to be in close association with the ER membrane (8, 13-16).
The occurrence of obesity is approaching epidemic proportions. Many of the diseases associated with obesity, namely diabetes, hepatic steatohepatitis and atherosclerosis are the result of inappropriate storage of fat. Thus, there is a need for means that can effectively reduce fat storage in human tissues.